Ibrance (Palbociclib)
Comments
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I think SusaninSF is on the Alpelisib (PI3K inhibitor) BYLieve trial. Alisertib is the Aurora A Inhibitor, currently also in trial. Looks like researchers forget there are other letters after "A"..
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Crap, Dee, you are right, I keep getting Alpelisib mixed up with Alisertib!!
But both drugs are of GREAT interest to us, which is probably why I am mixing them.
Ann, what drug are you taking? Is it Alisertib?
The reason why they both are so important, is that Alisertib is an AURORA A kinase inhibitor.
Alpelisib, as we know, is an inhibitor of PI3K kinase.
However, a study at UCSF was looking into why it was so hard to find a super-effective PI3K inhibitor, and they tried mixing the drug with every other kinase inhibitor that they could get their hands on, and low and behold they got a massive synergy when the combined the two drugs (PI3K inhibitor with Aurora A kinase inhibitor). By far and away, that combination was the strongest (but remember this is preclinical data, in mice)
But no trials yet testing them in combination- its hard enough for Alpelisib alone (or with Faslodex) with the drops in blood sugar and rashes.
So, Ann, if you are taking Alisertib, then yeah your side effects would be different. Can you post a link to the clinical trial you are on?
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And yes, eventually they will settle on the combination we all should have been taking for the cure:
Alpelisib- Alisertib-Abemaciclib-Atezoluzimab-Aromasin
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Penny, the combo trial I was hoping they would get going on was to combine Alisertib with Alpelisib (not Affinitor, that is the one "A" drug I'm not so keen to try), although you are correct in remembering that the article did say it should work well in combination with Affinitor/Everolimus as well- anyway here's the article talking about how good the combo was in the lab expts:
https://www.ucsf.edu/news/2018/06/410906/combinati...
The hope would be if the combo works better than either alone, then it should be possible to use lower levels of Alpelisib and circumvent some of the SEs. But hey, maybe Alisertib works well on its own for MBC?
Ann: Is this your trial?
https://clinicaltrials.gov/ct2/show/NCT02860000PS I am so grateful you posted on this trial- five out of six patients responded?! And now you? That's fabulous!
PPS Also, if not used in combination, the article indicates that this drug (Alisertib) should be a good one to try after progression on Affinitor or Alpelisib...
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Wow thanks so much everyone for all those replies and info!!!
Ann yay! that's so exciting you are getting that response and, as Cure-ios already said -- 5 out of 6 really sounds terrific. I've had high hopes for Alisertib since I read the research last June though it sounds like I'm in very good company in getting it confused with Alpelisib. I only recently realized that I was following news the wrong trial!
You guys are the best!!!
Sandy nice to see you again -- I always think about how close we are in the timing of our journey.
And Daniel thanks for jumping in. How is your wife doing?
South Jersey sorry I haven't seen anything on that but I'll let you know if I do
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Here’s the link to the Alisertib (Aurora Kinase inhibitor) trial:
https://clinicaltrials.gov/ct2/show/NCT02219789
This link is anabstract from phase 1:
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sorry - the trial link In my previous post was for phase - I guess. Cure-ious yours is the right one: https://clinicaltrials.gov/ct2/show/NCT02860000 - it is only at Mayo Clinic in Rochester MN
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Ann, although the numbers are small (because it was phase 1), a starting PFS at 12.4 months (with people still on the drug it will go higher) and response rate of 78% with no grade 3 toxicities is pretty much kickass!
They say upregulation of AuroraA kinase is common way for the cancer to become AI resistant, so I guess it is either VERY common, or they would have gotten even better numbers had they selected for patients that over-express AuroraA.
I hope others pick up on this trial!
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Cure-ious- do u happen to know how they determine overexpression of AurouraK - though genetic testing or other?I have not heard that is something tested for.
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I have a dumb question: which are the Al drugs to which we become or may become resistant?
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And another question: my pathology slides from my most recent bone biopsy (and maybe from the earlier on 2 years ago) were sent to Foundation One for testing. I am to get results on February 8th from my onc. Would that specific level of testing address the upregulation of AuroraA kinase and/or the PI3K kinase? I'm totally confused, and you are are sailing along with wonderful understanding! Thanks!
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Sure Joyner, I was thinking of you guys moving from I/F to Xeloda,AA, or other things- Ann progressed on I/F but then moved to Halaven, which didn't help, whereas she did respond (six months so far) to this Aurora A kinase inhibitor
So that I don't confuse people, it seems that the trial does NOT require that you show any test for AuroraA kinase expression (Ann can weigh in if there were any testing requirements for the trial?)- my comment was its impressive to have such a high response rate when they apparently did not even test for Aurora A expression or activity in the cancer It might be part of the PI3K pathway, I don't know but will look that up. To me the exciting thing is something new to consider after I/F fails, so we can consider Affinitor (FDA approved), Alpelisib (hopefully will be FDA approved this year) and Alisertib (can only get in a trial). Of those 3 drugs, maybe the Alisertib has the fewer side effects? Its too early to know because too few patients have had it- but the numbers for Alisertib might end up being better even if its just because fewer people have to drop out of the trial . How great to have another possible drug targeted therapy alternative to IV chemo/!! (PS I don't know the answers to your genetic tests since I haven't had any testing done so far)
The only consideration is this trial is only offered at Mayo Clinic (thus far), but anyway kudos to them for deciding to pick up this trial on their own and then have it look so promising!
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The genetic testing I had done was through TEMPUS - which I believe is like Foundation one. That was how I found out about the PIK3CA and other mutations. Not sure how they test for for AuouraK
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I read the published report for phase 1 from Mayo Clinic, the most common side effect is neutropenia (like with Ibrance) and they are experimenting with different dosing regimens to see if that makes a difference. Most on the trial had failed Faslodex, about half had failed AA, yet most responded to Alisertib. One patient of the ten was still on the drug at 31 months! They say it looks as good or better than some other post-I/F treatments but emphasize that they need to get a much larger numbers of patients into the trial to get hard numbers for PFS, etc.
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There were no trial requirements as far as genetic mutations, amplifications, etc.. they did take tubes and tubes of blood though. An initial biopsy is required along with one at one month and then at the time of progression. Monthly blood draws for kidney, liver and hematology along with MO visit.
I believe a couple of the Mayo research doctors like Haddad have been working with this drug for a while now. Guess it is my thought that an institution like Mayo wouldn’t take on this trial and drug if it wasn’t somewhat promising. I am surprised they don’t have more trial locations which would certainly limit the # of patients and slow down the trial to clinic time. If results are as good as they say so far, hope they can open more sites and then fast track it. Likewise hoping Alpelisib gets to the clinic soon!
Just gonna add this link which shows additional research that is being done on Alisertib to make it even better- at least that’s what I think it says - trying to read all the technical jargon 🙃...https://www.thehindu.com/sci-tech/science/iiser-pune-uses-nanovesicles-to-improve-cancer-drug-delivery/article24483351.ece
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Speaking of technical jargon here's the link to the article that prompted me to ask the question yesterday about any news of a trial combining Alisertib and Affinator. My DH is mind of obsessed with finding these research leads ... and I'm not going to complain. :-)
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Joyner, to answer one of your questions I think there are three AIs -- i.e. aromatese inhibitors -- letrozole, anatrozole, and extemestane. Falsodex (your original combo drug) was an estrogen downregulator. Cure-ious has explained the different pathways they hit -- and what pathway needs to be hit when resistance develops -- infinitely better than I can.
What I take away from all of this is that our options are growing. It's very exciting!
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penny- tried to search for trials for Alisertib and Affinitor but didn’t find anything but did come up with this which show more sites for the Alisertib and Fulvestrant trial! I hope this is current information:
https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/alisertib
Nice if they would add an arm to test Affinitor and one for Alpelisip
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Awesomw Ann. Thanks
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I wonder if one of the sites for this study is UCSF- I don't know if they would take bone only mets patients since they can't really biopsy anything very easily or accurately.
What do people know about going from ER/PR+ to ER+/Pr- with mets? I have heard all sorts of things-
1.) it is not accurate if the Pr- was discovered on bone mets only
2.) it makes the cancer more aggressive, less likely to respond to treatment.
3.) It makes it more likely to respond to treatment
4.) If you are Pr- tamoxifen won't work.
Thanks for any info
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Penny, seems like I was the one who started the name confusion. I read A and ran with Alpelisib. My wife is doing ok at the moment, thank you for asking.
I totally understand your DH. I am constantly on the prowl for new breakthrough studies hoping to be prepared in case of future need for therapy changes.
Cure-ious, thank you for your precious insights!
Nkb - I would also like for someone to shed light on that very topic. My wife's primary mass bx came back >90% positive for both ER and PR. She then underwent surgery on her femur met and the biopsy came with 70% ER and negative for PR. Onc didnt seem fazed.
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My y90 was done while I had mets in my chest and lung. So, yes it's absolutely okay to have y90 if you have other organ mets.
It didn't take long, one month, for AA to fail me. The SE were too horrible. The most recent one is the spike in my blood sugars. It's so bad it caused my doc to put me on insulin. Previously it had been controlled with 3 non insulin meds.
So tomorrow I get to tell my doctor I am intolerant of the SE. I don't know what she'll change me to. I also get the results of my brain MRI.
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NkB and Daniel, I am similar situation, my mets from bone biopsy came back ER+PR- HER2-. Assuming that is correct, it indicaes loss of PR (progesterone receptor) expression, which is often seen in more aggessive luminal B cancers. Because PR is turned on by ER and estrogen, it can indicate that the estrogen signaling or dependence of the cancer is not great, and that it might become resistant to anti-estrogen therapy more quickly than other cancers. But Zarovka found a part of a paper from the Ibrance studies that showed that PR-negative cancers are helped more by Ibrance, so that might be a trade-off. Anyway, several of us are hanging around on IF for awhile, so it doesn't worry me much anymore. And also bone biopsy samples not very sensitive or accurate, so there is that too..
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Grannax2, did your MO think your lung side effect on Afinitor was pneumonitis? I am surprised that a lowered dose was not offered to keep you on the mTOR inhibitor since you have the ESR mutation. Do you have the PIC3K mutation?
Xeloda next? Maybe time for second opinion for next drug choice or clinical trial? Will you be scanned to see how your liver is currently doing? Your lung mets stable?
You have been so publicly open about your treatment journey, just worried about you not getting the best options.
Brain MRI..did I miss something. I need to go find where you are posting. Lordy.
You have your BCO friends behind you at every step.
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Grannax- I am in the same boat with you. I had to start insulin yesterday. Before I took the first dose, my blood sugar was 572! I'm going to give it a week or so to see how well my sugar is controlled on the insulin. If I find that I can't manage to keep it under much better control, I will be off to the next treatment plan also...
Prayers for all.....
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Hi all - I was ER/PR 90% (and Her2+) at original dx and my single bone met biopsy came up ER 60%, PR - and still Her2+.
I spent quite some time worrying about this PR- thing. I read a lot of conflicting info and found myself focused on the negative aspects. My MO finally said to me - “Let it go. The truth is we have no idea how it impacts things and if it is a good thing or a bad thing and under what conditions. So chill!” And I haven’t thought much about it since! :-)
I love that he knows how to handle me.
Love to all,
Lauren
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sorry i haven’t posted in a while but since the blood clots life is crazy. i feel like my job is thinking “here we go this is it for her being able to work” my husband says it’s all in my head.
in january i had two blood clots in my left cheek of my bottom they all said this is unusual. when i was leaving work one thursday i picked up my purse and felt like i pulled a muscle in my bottom. that night i took ibuprofen and had no pain the next day. thought it was a se from the ibrance. saturday i did some house work and that afternoon the pain hit with a vengeance and went down the front of my leg to my knee. i took more ibuprofen but this time it didn’t take the pain away. sunday i was fine until i walked to the restroom and the pain was sooooo bad. i went to the er and they were going to send me home with a pulled muscle but decided to do a ct scan since my cancer was in that hip. that’s when they found them. i will be on blood thinners the rest of my life
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Grannax- Praying for you with your next treatment plan and the brain MRI results.
Masonsmawmaw- Prayers for you too with the high blood sugars and going to another treatment.
It is great so many on here on looking into the latest info for all the rest of us!!!!
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Well, had my appt with new Onc this am. Didn't actually meet him, his recommendations and concerns were translated to me thru Carla, Nur Prac whom I adore. To quickly recap my history, original breast tumor never removed, was put on Amiridex (sp) to shrink. Progression. By 13 mos. Mets in bones, lungs. Was put on Ful/IB. At 3mos CT bone scans showed original tumor had shrink slightly as had lymph node. But more bone nodules and bone mets had enlarged. Then just 2 weeks ago during another biopsy a second breast tumor was found. With a sonogram. So definite progression. So, I'm off Ibrance/Ful.
I really wanted to plead to stay on Ful/I longer but I did not. The reason being is that the breast tumor (2nd) has grown thru my skin. It's about the size of a half dollar. Starts with small little growths and then merge together. My fear, as well as my Onc's is that this is going to ulcerate. I will not be able to handle that, I know my limitations.
Onc. said he's not sure that anti hormonals have failed but they are not working quickly enough for the breast issue.
Plan TAXOL for 3 mos. Preferred. Said I could do it with no port. Or,
Xeloda time unspecified. They want to decrease tumor load in that breast quickly and they are of the opinion that TAXOL is best choice.
Carla also said that TAXOL is one of the easier chemos, I could do it without a port and less side effects than the Xeloda. Claimed probably no hair lose and I could drive myself. I live alone.
After Shrinkage the plan is back on anti-hormonals. I know what my choice should be, but I'm terrified of IV chemo. So, I need to talk with my 3 adult boys and call in couple days and let her know of my plan. Dang, it's been a long month. Prayers for best decision needed. Hugs to All Sue
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Oh Onc. wants to use tamoxifen after the chemo treatment. ( I would have edited and added this but, every time I try that I lose all my type)
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